TGF-β1-Containing Exosomes from Injured Epithelial Cells Activate Fibroblasts to Initiate Tissue Regenerative Responses and Fibrosis

被引：359

作者：

Borges, Fernanda T. ^{[1
]}

Melo, Sonia A. ^{[1
,2
]}

Oezdemir, Berna C. ^{[1
,2
]}

Kato, Noritoshi ^{[1
]}

Revuelta, Ignacio ^{[1
]}

Miller, Caroline A. ^{[3
]}

Gattone, Vincent H., II ^{[3
]}

LeBleu, Valerie S. ^{[1
]}

Kalluri, Raghu ^{[1
,2
,4
,5
]}

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Matrix Biol,Dept Med, Boston, MA 02215 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Metastasis Res Ctr, Houston, TX 77030 USA

[3] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN USA

[4] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA

[5] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2013年 / 24卷 / 03期

基金：

美国国家卫生研究院;

关键词：

CHRONIC KIDNEY-DISEASE; MOLECULES; GRANULES; HYPOXIA;

D O I：

10.1681/ASN.2012101031

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Hypoxia is associated with tissue injury and fibrosis but its functional role in fibroblast activation and tissue repair/regeneration is unknown. Using kidney injury as a model system, we demonstrate that injured epithelial cells produce an increased number of exosomes with defined genetic information to activate fibroblasts. Exosonnes released by injured epithelial cells promote proliferation, a-smooth muscle actin expression, F-actin expression, and type I collagen production in fibroblasts. Fibroblast activation is dependent on exosomes delivering TGF-beta 1 mRNA among other yet to be identified moieties. This study suggests that TGF-beta 1 mRNA transported by exosomes constitutes a rapid response to initiate tissue repair/regenerative responses and activation of fibroblasts when resident parenchyma is injured. The results also inform potential utility of exosome-targeted therapies to control tissue fibrosis. J Am Soc Nephrol 24: 385-392, 2013. doi: 10.1681/ASN.2012101031

引用

页码：385 / 392

页数：8

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